The Effects of ATLAS Therapy on Nitric Oxide Bioavailability in Patients With Intermittent Claudication

NCT ID: NCT04800692

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-15
• Study Completion Date: 2027-12-31

Brief Summary

This study will focus on people with claudication from peripheral arterial disease. The investigators are researching whether a multicomponent therapeutic can increase the production of Nitric Oxide in the blood and whether that leads to an improvement in pain free walking distance and overall physical activity.

Detailed Description

The primary objective of this study is to show that ATLAS Therapy, (L-Arginine; Tetrahydrobiopterin; L-Ascorbate) is bioavailable in humans and exerts a measurable effect on its in vivo biological signature, Flow Mediated Vasodilation (FMD) in people with intermittent claudication caused by peripheral arterial disease. This will be a Phase I / dose finding study. All subjects will receive 2 different drug doses of the Kuvan the first 45 days they will receive 10 mg/kg/day. The second 45 days they will receive 20/mg/kg/day.

Conditions

Claudication, Intermittent; Peripheral Artery Disease; Peripheral Vascular Diseases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Tetrahydrobiopterin Dose 1 (Day 0 to 44)

All subjects will receive 3300mg l-Ascorbate , l-Arginine 3400mg and 10mg/kg of Tetrahydrobiopterin once a day.

Group Type: EXPERIMENTAL

Tetrahydrobiopterin 10 mg/kg

Intervention Type: DRUG

10mg/kg of Tetrahydrobiopterin daily.

L-Ascorbate

Intervention Type: DRUG

3300 mg of l-ascorbate once daily

L-Arginine

Intervention Type: DRUG

3400mg of l-arginine once daily

Tetrahydrobiopterin Dose 2 (Day 45 to 90)

All subjects will receive 3300mg l-Ascorbate, l-Arginine 3400mg and 20mg/kg of Tetrahydrobiopterin once a day.

Group Type: EXPERIMENTAL

Tetrahydrobiopterin 20 mg/kg

Intervention Type: DRUG

20mg/kg of Tetrahydrobiopterin daily.

L-Ascorbate

Intervention Type: DRUG

3300 mg of l-ascorbate once daily

L-Arginine

Intervention Type: DRUG

3400mg of l-arginine once daily

Interventions

Tetrahydrobiopterin 10 mg/kg

10mg/kg of Tetrahydrobiopterin daily.

Intervention Type: DRUG

Tetrahydrobiopterin 20 mg/kg

20mg/kg of Tetrahydrobiopterin daily.

Intervention Type: DRUG

L-Ascorbate

3300 mg of l-ascorbate once daily

Intervention Type: DRUG

L-Arginine

3400mg of l-arginine once daily

Intervention Type: DRUG

Other Intervention Names

sapropterin; kuvan; sapropterin; kuvan

Eligibility Criteria

Inclusion Criteria

• PAD as demonstrated by an ABI <0 .9 in one leg or TBI less than <0.7 in patients with an ABI >1.3 (non compressible vessels)
• Rutherford Classification II, III
• Age >18 years old
• Willingness to discontinue phosphodiesterase (PDE) 5 inhibitors such as Viagra, Cialis, Levitra, Revatio
• Willingness to discontinue phosphodiesterase (PDE) 3inhibitors cilostazol, milrinone or Vesnarinone
• Willing and able to comply with all study procedures
• Willing and able to provide informed consent
• Sexually active subjects willing to use an acceptable method of contraception while participating in the study

Exclusion Criteria

• Hypotension defined as a systolic blood pressure less than 100mmhg systolic at screening or baseline visit
• Critical Leg Ischemia (Rutherford Classification IV, V, VI)
• Surgical intervention to alleviate symptoms of claudication in the study leg within the past 6 months or any endovascular interventions within 3 months or who is scheduled to undergo surgical revascularization in the next 6 month
• Walking limited by reasons other than claudication (e.g. arthritis, lung disease, severe neuropathy, lower extremity amputation except single digits)
• Serum creatinine >1.5mg/dl or Hepatic enzymes >2X the upper limit of normal
• Serum potassium greater than 5.0 or use of a potassium sparing diuretic at screening
• Pregnant, breast feeding or planning to become pregnant (subject or partner) at any time during the study.
• Myocardial Infarction, Cerebrovascular Accident or deep vein thrombosis within 12 months of screening
• Known history of nephrolithiasis
• History of ever having a seizure
• Concurrent disease or condition that would interfere with study participation or safety such as bleeding disorders, organ transplant, long term immunosuppression (excluding inhaled steroids), current neoplasm or severe gastroesophageal reflux
• History of vertigo or syncope within the past 10 years
• Enrollment in another drug or device study within 30 days of screening
• Required treatment with a drug known to inhibit folate metabolism (e.g. Methotrexate)
• Taking any of the following medications; PDE3 Inhibitors, PDE5 inhibitors, trental, nitrates, ginkgo biloba, levodopa, warfarin,
• Axillary lymph node dissection
• Presence of an amputation except single digits in either leg
• Preexisting illness that limits ambulation such as severe COPD, class III-IV heart failure, severe arthritis or back pain
• Glucose-6-dehydrogenase deficiency

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Louis Messina

OTHER

Sponsor Role: lead

Responsible Party

Louis Messina

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Louis M Messina, MD

Role: PRINCIPAL_INVESTIGATOR

UMASS Medical School

Locations

UMASS Memorial Healthcare - University Campus

Worcester, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Shauneen Valliere, MSN

Role: CONTACT

shauneen.valliere@umassmed.edu

508-856-1767

Mollynda McArthur, MS

Role: CONTACT

mollynda.mcarthur2@umassmed.edu

508-856-2820

Facility Contacts

Shauneen Valliere, MSN

Role: primary

shauneen.valliere@umassmed.edu

508-856-1767

Mollynda McArthur, MS

Role: backup

mollynda.mcarthur2@umassmed.edu

508-856-2820

Other Identifiers

H00012734

Identifier Type: -

Identifier Source: org_study_id